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July 14, 2009 -- Women who are on hormone therapy or who have used it in the recent past are at higher risk of ovarian cancer than women who have never been on hormone therapy, a new study shows.

The increase in risk was found regardless of the hormone dose or formulation, whether hormones were taken by mouth, transdermal patch, or vaginally, or whether the treatment included just estrogen or estrogen and progestin, the researchers say.

The study confirms earlier research linking hormone therapy and ovarian cancer, but the new study is believed to be the largest and most detailed study to date on the topic, says the study's lead author Lina Morch, a researcher at Rigshospitalet, Copenhagen University in Denmark.

"Our study underlines that postmenopausal hormones increase the risk for ovarian cancer," she tells WebMD in an email interview. "Furthermore, this study suggests that no type of hormone seems safe regarding the risk of ovarian cancer -- even at use below four years the risk is increased." Some previous research had not found an increased cancer risk with hormone use of less than five years.

Both estrogen alone and combination therapy that adds progestin boosted risk, Morch says. Her study is published in The Journal of the American Medical Association.

Ovarian Cancer and Hormones

In the study, Morch and her team evaluated more than 909,000 Danish women, ages 50 to 79, who were on national Danish registers. After an average of eight years of follow-up, 3,068 cases of ovarian cancer were found. At the end of the study, 63% of the women were never-users of hormone therapy and 9% current users.

Compared to never users, current hormone therapy users had an overall 38% increased risk of ovarian cancer.

Put another way: for every 8,300 women on hormone therapy per year, one extra case of ovarian cancer could be attributed to hormone therapy.

Risk did decline in past users as the years of being hormone-free increased. By the time past users had been off hormone therapy for two years, their risk of ovarian cancer was about the same as for non-users, Morch found. By the time women had been off the hormone therapy for more than six years, the risk of ovarian cancer was nearly 40% less in these past users than the never users. Morch says that finding is based on a low number of women who had quit hormone therapy for more than six years. ''What is important is the risk declines in former users with increasing time since last use,'' she says.

For those currently on hormone therapy, the risk of getting ovarian cancer didn't differ much among the various therapies, doses, or administration, Morch found.

''Ovarian cancer is among the most lethal of gynecologic cancers," Morch says. "The five-year survival rates are 40%." To complicate the issue, ovarian cancer is difficult to detect, and thus often not found until it is in advanced stages.

Previous research has found that current use of hormones raises ovarian cancer risk by 30% compared with no hormone use, with the risk of estrogen-only therapy sometimes found to be higher than combined therapy.

''This study supports an approximately similar increased risk for ovarian cancer disregarding the hormone type," she says.

This year, 21,550 new cases of ovarian cancer are expected in the U.S., with an estimated 14,600 deaths from the disease, according to American Cancer Society estimates.

Second Opinion

"It's a well done study," says Andrew Li, MD, a gynecologic oncologist at Cedars-Sinai Medical Center, Los Angeles, who reviewed the study for WebMD. "Their findings are in line with what other people report," says Li, who is also an assistant clinical professor of obstetrics and gynecology at the University California Los Angeles' David Geffen School of Medicine.

Like most research, the study has limitations that may have affected the results, Li says, and the authors also acknowledge this. Among the limitations are that the researchers didn't adjust for age at menopause or use of birth control pills; birth control pill use and early natural menopause both reduce ovarian cancer risk.

The main contribution of the new study is to look at large numbers of women who took different types of hormone therapy and determine which type or types carry risk, says Shelley Tworoger, PhD, an assistant professor of medicine and epidemiology at the Harvard School of Medicine and School of Public Health, who has also published her research on hormone therapy and ovarian cancer risk. "The real contribution [of the new study] is that the combined regimen also increases the risk of ovarian cancer," she says. In her research, Tworoger found that estrogen-only therapy boosted risk and a suggestion of an increased risk with estrogen and progestin therapy.

The new research basically confirms what has been shown in previous studies, says Corrado Altomare, MD, senior director of global medical affairs for Wyeth Pharmaceuticals in Collegeville, Pa. "This finding doesn't really change what we know," he tells WebMD. "We actually have a warning in our label about ovarian cancer."

Wyeth's label summarizes the risks found for ovarian cancer with hormone use, using information from various studies.

The best advice for women? "If a woman has a special predisposition for ovarian cancer, she should consider not taking hormones," Morch says. Past users, she says, can be reassured that their risk declines to that of never users after being off the therapy for two years.

Even with the link to ovarian cancer, Morch says, she is not saying hormone therapy should never be used. "Hormones may still have a therapeutic place in women with severe perimenopausal symptoms, and among women going into premature menopause," she says.

Women should talk to their doctor about hormone use, Li says, so the decision can be based on individual risk factors and medical history.